Ni Haibo, Rui Qin, Lin Xiaolong, Li Di, Liu Huixiang, Chen Gang
Department of Neurosurgery, Zhangjiagang First People's Hospital, Suzhou, China.
Department of Laboratory, Zhangjiagang First People's Hospital, Suzhou, China.
Front Neurosci. 2019 Jun 26;13:674. doi: 10.3389/fnins.2019.00674. eCollection 2019.
Inflammation and programmed necrosis (necroptosis) are the two hallmark pathological changes after traumatic brain injury (TBI) that contribute to aggravated brain damage. 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) has been shown to exert both anti-inflammatory and programmed cell death effects. Therefore, the aim of the present study was to evaluate the potential beneficial effects of 2-BFI in a rat model of TBI induced by a weight-drop device. 2-BFI or vehicle was given via intraperitoneal injection starting at 30 min post trauma and then twice daily for three consecutive days. Following a neurofunctional test at 72 h after injury, histological, molecular, and immunohistochemistry analyses were performed on the pericontusional areas of the brain. 2-BFI treatment significantly attenuated neurological deficits, brain edema and blood-brain barrier permeability after TBI. Also, treatment with 2-BFI significantly reduced microglial activation, neutrophil infiltration, and proinflammatory cytokine interleukin (IL)-1β secretion, which is related to nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation after TBI. In addition, 2-BFI treatment markedly reduced cortical tissue loss as well as repressed TBI-induced increases in necroptosis and necroptosis-associated proteins, including receptor-interacting protein (RIP1), RIP3, and mixed linkage kinase domain-like (MLKL) in the pericontusional brain tissue. Taken together, these findings indicate that 2-BFI may be an effective neuroprotectant after brain trauma and warrants further study.
炎症和程序性坏死（坏死性凋亡）是创伤性脑损伤（TBI）后的两个标志性病理变化，会导致脑损伤加重。2-（2-苯并呋喃基）-2-咪唑啉（2-BFI）已被证明具有抗炎和程序性细胞死亡作用。因此，本研究的目的是评估2-BFI在重物坠落装置诱导的TBI大鼠模型中的潜在有益作用。在创伤后30分钟开始通过腹腔注射给予2-BFI或赋形剂，然后连续三天每天两次。在损伤后72小时进行神经功能测试后，对脑挫伤周围区域进行组织学、分子和免疫组织化学分析。2-BFI治疗显著减轻了TBI后的神经功能缺损、脑水肿和血脑屏障通透性。此外，2-BFI治疗显著降低了小胶质细胞活化、中性粒细胞浸润和促炎细胞因子白细胞介素（IL）-1β分泌，这与TBI后核苷酸结合寡聚化结构域样受体家族含吡啉结构域3（NLRP3）炎性小体活化有关。此外，2-BFI治疗显著减少了皮质组织损失，并抑制了TBI诱导的挫伤周围脑组织中坏死性凋亡及坏死性凋亡相关蛋白的增加，包括受体相互作用蛋白（RIP1）、RIP3和混合连接激酶结构域样蛋白（MLKL）。综上所述，这些发现表明2-BFI可能是脑外伤后一种有效的神经保护剂，值得进一步研究。
